title: A glutathione derivative with chelating and in vitro neuroprotective activities: synthesis, physicochemical properties, and biological evaluation.
abstract: Metal-ion dysregulation and oxidative stress have been linked to the progressive neurological decline associated with neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Herein we report the synthesis and chelating, antioxidant, and in vitro neuroprotective activities of a novel derivative of glutathione, GS(HQ)H, endowed with an 8-hydroxyquinoline group as a metal-chelating moiety. In vitro results showed that GS(HQ)H may be stable enough to be absorbed unmodified and arrive intact to the blood-brain barrier, that it may be able to remove Cu(II) and Zn(II) from the Aβ peptide without causing any copper or zinc depletion in vivo, and that it protects SHSY-5Y human neuroblastoma cells against H2 O2 - and 6-OHDA-induced damage. Together, these findings suggest that GS(HQ)H could be a potential neuroprotective agent for the treatment of neurodegenerative diseases in which a lack of metal homeostasis has been reported as a key factor.
authors.affiliation: Department of Pharmacy, University "G. D'Annunzio", Via dei Vestini 31, 66100 Chieti (Italy). cacciatore@unich.it.
authors.forename: Ivana
authors.initials: I
authors.lastname: Cacciatore
authors.forename: Catia
authors.initials: C
authors.lastname: Cornacchia
authors.forename: Erika
authors.initials: E
authors.lastname: Fornasari
authors.forename: Leonardo
authors.initials: L
authors.lastname: Baldassarre
authors.forename: Francesco
authors.initials: F
authors.lastname: Pinnen
authors.forename: Piera
authors.initials: P
authors.lastname: Sozio
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Stefano
authors.forename: Lisa
authors.initials: L
authors.lastname: Marinelli
authors.forename: Annalisa
authors.initials: A
authors.lastname: Dean
authors.forename: Stefania
authors.initials: S
authors.lastname: Fulle
authors.forename: Ester Sara
authors.initials: ES
authors.lastname: Di Filippo
authors.forename: Rita Maria Laura
authors.initials: RM
authors.lastname: La Rovere
authors.forename: Antonia
authors.initials: A
authors.lastname: Patruno
authors.forename: Alessio
authors.initials: A
authors.lastname: Ferrone
authors.forename: Valerio
authors.initials: V
authors.lastname: Di Marco
mesh_terms: D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005978:Glutathione / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015394:Molecular Structure; D009447:Neuroblastoma / Q000473:pathology; D018696:Neuroprotective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015125:Oxyquinoline / Q000737:chemistry; D017382:Reactive Oxygen Species; D012995:Solubility
chemical_list: D000975:Antioxidants; D002614:Chelating Agents; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D015125:Oxyquinoline; D005978:Glutathione
keywords: 8-hydroxyquinolines; antioxidants; chelation therapy; glutathione; neurodegenerative diseases; peptides